Genetic Variant MTAP:c.33+142C>G (chr9-21802923-C-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001396040.1(MTAP):c.57C>G(p.Leu19Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 1,437,612 control chromosomes in the GnomAD database, including 1,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 68 hom., cov: 28)

Exomes 𝑓: 0.031 ( 986 hom. )

Consequence

MTAP
NM_001396040.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0110

Variant links:

Genes affected

MTAP (HGNC:7413): (methylthioadenosine phosphorylase) This gene encodes an enzyme that plays a major role in polyamine metabolism and is important for the salvage pathway of both adenine and methionine. The encoded enzyme is deficient in many cancers. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2021]

MTAP links:

ENSG00000264545 (HGNC:):

ENSG00000264545 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 9-21802923-C-G is Benign according to our data. Variant chr9-21802923-C-G is described in ClinVar as [Benign]. Clinvar id is 1223355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.011 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTAP	NM_002451.4 link	c.33+142C>G		intron_variant	Intron 1 of 7	ENST00000644715.2	NP_002442.2	Q13126-1A0A384ME80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTAP	ENST00000644715.2 link	c.33+142C>G		intron_variant	Intron 1 of 7		NM_002451.4	ENSP00000494373.1		Q13126-1

Frequencies

GnomAD3 genomes

AF:

0.0236

AC:

3513

AN:

149060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00457

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0208

Gnomad ASJ

AF:

0.0275

Gnomad EAS

AF:

0.0826

Gnomad SAS

AF:

0.0771

Gnomad FIN

AF:

0.0370

Gnomad MID

AF:

0.00962

Gnomad NFE

AF:

0.0257

Gnomad OTH

AF:

0.0256

GnomAD2 exomes

AF:

0.0364

AC:

1731

AN:

47538

AF XY:

0.0391

show subpopulations

Gnomad AFR exome

AF:

0.00396

Gnomad AMR exome

AF:

0.0137

Gnomad ASJ exome

AF:

0.0303

Gnomad EAS exome

AF:

0.0770

Gnomad FIN exome

AF:

0.0325

Gnomad NFE exome

AF:

0.0265

Gnomad OTH exome

AF:

0.0320

GnomAD4 exome

AF:

0.0310

AC:

39939

AN:

1288436

Hom.:

986

Cov.:

AF XY:

0.0325

AC XY:

20465

AN XY:

630306

show subpopulations

African (AFR)

AF:

0.00298

AC:

AN:

25822

American (AMR)

AF:

0.0141

AC:

258

AN:

18236

Ashkenazi Jewish (ASJ)

AF:

0.0314

AC:

582

AN:

18512

East Asian (EAS)

AF:

0.111

AC:

3671

AN:

33024

South Asian (SAS)

AF:

0.0775

AC:

4813

AN:

62094

European-Finnish (FIN)

AF:

0.0348

AC:

1183

AN:

33952

Middle Eastern (MID)

AF:

0.0221

AC:

AN:

3664

European-Non Finnish (NFE)

AF:

0.0263

AC:

27367

AN:

1039732

Other (OTH)

AF:

0.0357

AC:

1907

AN:

53400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

2008

4015

6023

8030

10038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0235

AC:

3508

AN:

149176

Hom.:

Cov.:

AF XY:

0.0254

AC XY:

1842

AN XY:

72636

show subpopulations

African (AFR)

AF:

0.00456

AC:

185

AN:

40600

American (AMR)

AF:

0.0208

AC:

309

AN:

14868

Ashkenazi Jewish (ASJ)

AF:

0.0275

AC:

AN:

3456

East Asian (EAS)

AF:

0.0824

AC:

409

AN:

4964

South Asian (SAS)

AF:

0.0767

AC:

353

AN:

4602

European-Finnish (FIN)

AF:

0.0370

AC:

370

AN:

10000

Middle Eastern (MID)

AF:

0.00690

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0257

AC:

1732

AN:

67432

Other (OTH)

AF:

0.0258

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

150

300

449

599

749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0243

Hom.:

Bravo

AF:

0.0196

Asia WGS

AF:

0.0900

AC:

312

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 21, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.2

(source)

DANN

Benign

0.73

PromoterAI

-0.0022

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

chr9-21802923-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over